The proposed research program utlizes various approaches within the disciplines of neurophysiology, neurochemistry, neuropharmacology, neuroanatomy, clinical neurology and electroencephalography to investigate a) the effects of epileptogenesis on brain development; b) relationships between injury to the developing brain and epileptogenesis; c) basic mechanisms for development of abnormal discharges in nerve cells; d) intrinsic mechanisms of modulation of excitability in the brain; and e) mechanims of action of convulsant and anticonvulsant drugs. The specific projects are: 1) Electrophysiology of Focal Epileptogenesis; 2) Anticonvulsant Pharmacology Studied In Vitro; 3) The Effects of Convulsant and Anticonvulsant Drugs on the Flux of Transmitter Amino Acids and Calcium in Brain Slices; 4) Effects of Epileptogenesis on Development of the Visual System; 5) Cellular Respiration and Epileptogenesis; and 6) Neonatal Seizures and Intraventricular Hemorrhage. The techniques to be used include cellular neurophysiological studies and iontophoresis of transmitters and other agents in hippocampal slices and spinal cord cell cultures; biochemical studies of putative amino acid transmitters and of cellular respiration in brain slices; extracellular recordings from visual pathways in immature animals; and clinical, EEG and radiologic evaluation of premature infants. Various models of epileptiform discharge will be examined including those produced by convulsant drugs, hyperthermia, and injection of iron salts. The long term goals of the program are to obtain information which will provide a better understanding of the pathogenesis of epileptiform discharge and insights which will lead to the development of rational new approaches to the prevention and treatment of epilepsy. The studies outlined will also contribute to our understanding of normal brain function.